1. Field of the Invention
Certain heterocyclic carboxamides, certain dihydro-1,4-disubstituted-quinoline-3-carboxylic acid amides; increasing the activity of the immune system; compounds per se, compositions thereof, methods of treating therewith.
2. Prior Art
The immune system of the body has long been the subject of concerted study. A vigorous search has been made for drugs which influence the immune system. Numerous drugs which suppress the activity of the immune system have been found and, more recently, some compounds have been discovered which increase the activity of the immune system of the body. Some of these rather recently-discovered compounds have been found capable of increasing the activity of the cell-mediated immunity of the host. The study of such compounds for such purpose is a branch of science which is still in its infancy, but of obviously great significance in view of the possibility of increasing immunity of a host by the administration of a drug. The far-reaching effect of such research is apparent to all skilled in the art.
To the best of our knowledge, no compounds even remotely related structurally to the active compounds of the present invention have been suggested as activators of cell-mediated immunity. The closest prior art known to us is represented by an article in the Indian Journal of Chemistry Vol. 17 B, May 1979, pp. 488-490 (reported in Chemical Abstracts 93 (1980), page 667, entry 2044220.) This article discloses compounds which are structurally related to the compounds claimed in the present application. These previously known compounds exhibit antiinflammatory activity as evidenced by a decrease in extent of carrageenan-induced edema in the carrageenan edema test.
The compounds according to the present invention, used for fundamentally different pharmacological purposes, do in fact, completely unexpectedly, increase the extent of carrageenan-induced edema in the test mentioned above (cf below and Table I of the present application), i.e. the compounds according to the present invention exhibit effects contrary to the effects exhibited by the previously known compounds.
Another type of compounds are disclosed in the Swiss Pat. Nos. 578,534, 578,535, 578,536, and 578,537, which relate to compounds suggested for different pharmacological uses, e.g. as antiinflammatory agents like the compounds disclosed in the Indian Journal of Chemistry These compounds differ from the active compounds of the present invention structurally in that they all possess a cycloaliphatic radical as substituent on the benzene ring of the quinoline nucleus, and in that they fail to show or suggest the essential substituents in the amide portion of the molecule. More remote structurally related compounds, namely 2,4-dihydroxyquinoline-3-carboxylic amides, have been reported in Japanese Pat. No. 6,823,948 (Cl. 16 E 432) of approximately Oct. 16, 1968, reported in Chemical Abstracts 70 (1969) on page 355, entry 57681x. The compounds there reported are said to be useful as bactericides, and no possible use in the activation of any immune system is suggested for those compounds.
Another type of quinoline-3-carboxylic amide wherein the amide portion of the molecule contains certain heterocyclic rings and which may also include 2,4-dihydroxy-substituted compounds, has been reported in the Swedish patent application No. 7700804-3, reported in Chemical Abstracts 87 (1977) on page 578, entry 152042z. The reported compounds are said to be useful as analgetics, and no possible use in the activation of any immune system is suggested for these compounds.